What is the strength of evidence supporting the use of spironolactone to aid diuresis in acute heart failure with impaired renal function?

Spironolactone in Acute Heart Failure with Kidney Injury

The evidence does not support the use of spironolactone to aid diuresis in acute heart failure with kidney injury. 1

Evidence Assessment

Efficacy in Acute Heart Failure with Renal Dysfunction

• The ATHENA-HF trial specifically evaluated high-dose spironolactone (100mg daily) in acute heart failure patients with varying degrees of renal function and found no incremental benefit on congestion relief, regardless of baseline renal function 1
• High-dose spironolactone did not improve N-terminal pro-B-type natriuretic peptide reduction or signs and symptoms of congestion compared to usual care, even in patients with risk factors for diuretic resistance 1
• Current European Society of Cardiology (ESC) guidelines mention that in acute heart failure, thiazides and aldosterone antagonists can be used in association with loop diuretics for diuretic resistance, but this is not specifically recommended for patients with kidney injury 2

Safety Concerns

• Spironolactone use in patients with heart failure and renal dysfunction is associated with a higher risk of hyperkalemia and acute kidney injury when added to loop diuretics 3
• The FDA label for spironolactone notes that patients with baseline serum creatinine >2.5 mg/dL were excluded from the landmark RALES trial, indicating limited evidence in patients with significant renal dysfunction 4
• Regular monitoring of renal function and serum electrolytes is mandatory when using mineralocorticoid receptor antagonists (MRAs) like spironolactone, with checks recommended at 1,4,8, and 12 weeks after initiation 2

Alternative Approaches for Diuresis in Acute Heart Failure with Kidney Injury

Loop Diuretic Strategy

• For patients with acute heart failure and impaired renal function, loop diuretics remain the cornerstone of therapy for congestion relief 2, 5
• Consider starting with a lower dose of IV furosemide (20mg) for new-onset heart failure patients or reducing the dose by 25-50% if AKI is significant 5
• For patients on chronic diuretic therapy, the initial IV dose should be at least equivalent to their home oral dose 5

Combination Diuretic Approach

• If diuretic resistance develops, consider dual nephron blockade with the addition of thiazide diuretics rather than spironolactone in patients with kidney injury 5
• Close monitoring of electrolytes and renal function is essential with this approach 5

Specific Situations Where Spironolactone May Be Considered

Chronic Heart Failure with Mild-Moderate Renal Dysfunction

• In chronic heart failure with reduced ejection fraction (HFrEF), spironolactone has shown mortality benefit in patients with moderate renal insufficiency (GFR 30-60 mL/min/1.73m²) 6
• A propensity-matched study showed that spironolactone was associated with improved 2-year survival in chronic heart failure outpatients with renal dysfunction (eGFR <60 mL/min/1.73m²), despite causing some worsening of renal function and increased potassium 7

Practical Recommendations if Using Spironolactone

• Start with a low dose (25mg once daily or on alternate days) 2
• Check renal function and electrolytes at 1,4,8, and 12 weeks; then at 6,9, and 12 months; and 6-monthly thereafter 2
• If potassium rises to >5.5 mmol/L, reduce dose to 25mg on alternate days 2
• If potassium rises to >6.0 mmol/L or creatinine rises to >221 μmol/L, stop spironolactone immediately 2

Conclusion

Based on the most recent evidence, particularly the ATHENA-HF trial, spironolactone does not provide incremental benefit for diuresis in acute heart failure with renal dysfunction and carries significant risks of hyperkalemia and worsening renal function. Loop diuretics, with careful dosing and monitoring, remain the primary approach for these patients.